Transition state tightness, nucleophilic

When Sn2 reactions are carried out on these substrates, rates are greatly increased for certain nucleophiles (e.g., halide or halide-like ions), but decreased or essentially unaffected by others. For example, a-Chloroaceto-phenone (PhCOCH2Cl) reacts with KI in acetone at 75°C 32,000 times faster than l-Chlorobutane, ° but a-bromoacetophenone reacts with the nucleophile triethylamine 0.14 times as fast as iodomethane. The reasons for this varying behavior are not clear, but those nucleophiles that form a tight transition state (one in which bond making and bond breaking have proceeded to about the same extent) are more likely to accelerate the reac-tion. ... 

It is significant to note that this reaction is highly unusual since the prochiral element resides entirely on the nucleophile. The chiral Lewis acid exerts control of en-antiofacial selectivity by proctor through tight control of the presumed heterocycloaddition transition state, Scheme 27. In effect, extremely high fidelity is necessary to orient the 2n component with respect to the 4ji component coordinated to the chiral Lewis acid. The factors that control the diastereoselectivity in the Mukaiyama Michael reaction of crotonylimides could also control enantioselectivity in the amination reaction. That selectivities on the order of 99% ee are observed in this reaction is testament to the level of control exerted by these catalysts. 

Second-order rate constants have been measured for the S 2 reactions of benzyl bromide and p-nitrobenzyl bromide with hydroxy nucleophiles. The values of (HOO )//c(HO ) are very small (1.3 and 1.2, respectively) for the two substrates. Thus the a-effect is very small and it is suggested that this may be due to the lack of tight a-bond formation at the transition state. 

In the high resolution crystal structure of the GTP form of Ras protein, a tightly bound water molecule is visible located in an optimal position for nucleophilic attack on the y-phosphate (Wittinghofer et al., 1993). The water molecule is fixed in a defined position by H-bridges with GIn61 and Hir35. As described in 5.4.4 for the a-subunits of the heterotrimeric G-proteins, GTP hydrolysis takes place by an in-line attack of the nucleophilic water molecule on the y-phosphate, for which a pentagonal, bipyramidal transition state is postulated. 

The alkali metals share many common features, yet differences in size, atomic number, ionization potential, and solvation energy leads to each element maintaining individual chemical characteristics. Among K, Na, and Li compounds, potassium compounds are more ionic and more nucleophilic. Potassium ions form loose or solvent-separated ion pairs with counteranions in polar solvents. Large potassium cations tend to stabilize delocalized (soft) anions in transition states. In contrast, lithium compounds are more covalent, more soluble in nonpolar solvents, usually existing as aggregates (tetramers and hexamers) in the form of tight ion pairs. Small lithium cations stabilize localized (hard) counteranions (see Lithium and lithium compounds). Sodium chemistry is intermediate between that of potassium and lithium (see Sodium and sodium alloys). 

Other phosphoryl transfer mechanisms are an associative, two-step mechanism (An + Dn) and a concerted mechanism (ANDN) with no intermediate. The AN+DN mechanism is an addition-elimination pathway in which a stable pentacoordinate intermediate, called a phosphorane, is formed. This mechanism occurs in some reactions of phosphate triesters and diesters, and has been speculated to occur in enzymatic reactions of monoesters. In the concerted ANDN mechanism, bond formation to the nucleophile and bond fission to the leaving group both occur in the transition state. This transition state could be loose or tight, depending upon the synchronicity between nucleophilic attack and leaving group departure. The concerted mechanism of Fig. 2 is drawn to indicate a loose transition state, typical of phosphate monoester reactions. 

Fig. 4 A transition state for phosphoryl transfer in which bond fission is ahead of bond formation to the phosphoryl acceptor (nucleophile) is loose, and resides in the lower right region. In the reverse situation a tight transition state results in the upper left region. If the sum of bond order to nucleophile plus leaving group is unity, the transition state will lie on the synchronicity diagonal.

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